Department of Laboratory Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
Department of Laboratory Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Cancer Research Institute, Seoul, Republic of Korea.
Cancer Genet. 2023 Aug;276-277:36-39. doi: 10.1016/j.cancergen.2023.07.003. Epub 2023 Jul 11.
KMT2A (11q23.3) gene rearrangements are found in acute leukemia and are associated with a poor or intermediate prognosis. MLLT10 is the fourth most common gene fusion partner for KMT2A. A reciprocal translocation t(10;11) is insufficient to produce an in-frame KMT2A/MLLT10 fusion, because the genes involved in the rearrangement have opposite transcriptional orientations. In order to bring KMT2A and MLLT10 into juxtaposition, complex rearrangements are required. Until now, conventional chromosome, fluorescence in situ hybridization (FISH), and reverse transcriptase-polymerase chain reaction (RT-PCR) studies have been used to detect KMT2A/MLLT10 fusions. However, conventional studies have limitations, such as poor and inconsistent resolution, when compared to next-generation sequencing (NGS). In this study, we report a pediatric patient with acute megakaryoblastic leukemia, in whom the cryptic KMT2A/MLLT10 fusion was not detected by KMT2A break-apart probe FISH and chromosome analysis, but detected by NGS. In this patient, NGS showed cryptic insertion of MLLT10 exons 9-24 into intron 9 of KMT2A, resulting in a KMT2A/MLLT10 fusion. Therefore, NGS is a valuable complementary option for the evaluation of structural aberrations, especially those with a cryptic size.
KMT2A（11q23.3）基因重排存在于急性白血病中，与预后不良或中等相关。MLLT10 是 KMT2A 的第四个最常见的基因融合伙伴。相互易位 t（10；11）不足以产生框内 KMT2A/MLLT10 融合，因为涉及重排的基因具有相反的转录方向。为了使 KMT2A 和 MLLT10 并列，需要复杂的重排。到目前为止，传统的染色体、荧光原位杂交（FISH）和逆转录聚合酶链反应（RT-PCR）研究已用于检测 KMT2A/MLLT10 融合。然而，与下一代测序（NGS）相比，传统研究存在分辨率差和不一致的局限性。在本研究中，我们报告了一例急性巨核细胞白血病患儿，该患儿的隐匿性 KMT2A/MLLT10 融合不能通过 KMT2A 断裂探针 FISH 和染色体分析检测到，但通过 NGS 检测到。在该患者中，NGS 显示 MLLT10 外显子 9-24 插入 KMT2A 内含子 9 中，导致 KMT2A/MLLT10 融合。因此，NGS 是评估结构异常的一种有价值的互补选择，尤其是那些隐匿性大小的异常。
